title: Structural basis of cargo recognitions for class V myosins.
abstract: Class V myosins (MyoV), the most studied unconventional myosins, recognize numerous cargos mainly via the motor's globular tail domain (GTD). Little is known regarding how MyoV-GTD recognizes such a diverse array of cargos specifically. Here, we solved the crystal structures of MyoVa-GTD in its apo-form and in complex with two distinct cargos, melanophilin and Rab interacting lysosomal protein-like 2. The apo-MyoVa-GTD structure indicates that most mutations found in patients with Griscelli syndrome, microvillus inclusion disease, or cancers or in "dilute" rodents likely impair the folding of GTD. The MyoVa-GTD/cargo complex structure reveals two distinct cargo-binding surfaces, one primarily via charge-charge interaction and the other mainly via hydrophobic interactions. Structural and biochemical analysis reveal the specific cargo-binding specificities of various isoforms of mammalian MyoV as well as very different cargo recognition mechanisms of MyoV between yeast and higher eukaryotes. The MyoVa-GTD structures resolved here provide a framework for future functional studies of vertebrate class V myosins.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Wei
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Liu
authors.forename: Cong
authors.initials: C
authors.lastname: Yu
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009218:Myosins / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D009218:Myosins
keywords: MLPH; RILPL2; granuphilin; myo5a; myosin V